1. Autism spectrum disorder and GABA levels in children with succinic semialdehyde dehydrogenase deficiency. Dev Med Child Neurol. 2024.

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2. Ahmad D, Small A, Gibson A, Kissoon N. Developmental outcomes in abusive head trauma. Semin Pediatr Neurol. 2024; 50: 101142.

Abusive head trauma (AHT) is associated with high mortality and poorer outcomes compared to accidental head injuries. The short and long-term developmental outcomes for AHT are not well identified. Variability in outcome measures, small sample sizes, difficulty in measuring domain-specific developmental skills, co-existence of comorbidities, genetic and environmental factors and high attrition rates all contribute to the challenges on providing data in this area. The objective of this article is to review the scientific literature on the developmental outcomes of AHT, highlighting factors that affect outcomes, the available assessment tools, and short and long-term developmental outcomes, recommended follow up, societal costs, and future opportunities for research. Authors searched OVID Medline and PubMed for articles published between 2013 and 2023 using the terms « abuse », « craniocerebral trauma » and « development ». Fifty-five records were included for this review. The data shows that injuries sustained from AHT result in a spectrum of outcomes ranging from normal development to death. There are more than 100 outcome assessment tools limiting the ability to compare studies. More than half of patients are left with disabilities post discharge. Gross motor and cognition/academics are the 2 most common domains studied. Advancement in surgical and neurocritical care management has influenced AHT outcomes. Close long-term follow up is recommended to maximize each child’s developmental potential, irrespective of the presence of disability at discharge. We suggest that future research should focus on adopting a consistent diagnostic and assessment approach and explore the social environmental factors that can affect recovery.

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3. Avó-Baião R, Vareda R, Lopes A. Comment on: « Maternal and Early-Life Exposure to Antibiotics and the Risk of Autism and Attention-Deficit Hyperactivity Disorder in Childhood: A Swedish Population-Based Cohort Study ». Drug Saf. 2024.

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4. Biswas MS, Roy SK, Hasan R, Pk MMU. The crucial role of the cerebellum in autism spectrum disorder: Neuroimaging, neurobiological, and anatomical insights. Health Sci Rep. 2024; 7(7): e2233.

BACKGROUND AND AIMS: Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by a wide range of symptoms and challenges. While ASD is primarily associated with atypical social and communicative behaviors, increasing research has pointed towards the involvement of various brain regions, including the cerebellum. This review article aims to provide a comprehensive overview of the role of cerebellar lobules in ASD, highlighting recent findings and potential therapeutic implications. METHODS: Using published articles found in PubMed, Scopus, and Google Scholar, we extracted pertinent data to complete this review work. We have searched for terms including anatomical insights, neuroimaging, neurobiological, and autism spectrum disorder. RESULTS: The intricate relationship between the cerebellum and other brain regions linked to ASD has been highlighted by neurobiological research, which has shown abnormalities in neurotransmitter systems and cerebellar circuitry. The relevance of the cerebellum in the pathophysiology of ASD has been further highlighted by anatomical studies that have revealed evidence of cerebellar abnormalities, including changes in volume, morphology, and connectivity. CONCLUSION: Thorough knowledge of the cerebellum’s function in ASD may lead to new understandings of the underlying mechanisms of the condition and make it easier to create interventions and treatments that are more specifically targeted at treating cerebellar dysfunction in ASD patients.

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5. Brusselaers N. Author’s Reply to Avó-Baião et al.’s Comment on « Maternal and Early-Life Exposure to Antibiotics and the Risk of Autism and Attention-Deficit Hyperactivity Disorder in Childhood: A Swedish Population-Based Cohort Study ». Drug Saf. 2024.

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6. Check J, Shuster C, Hofheimer J, Camerota M, Dansereau LM, Smith LM, Carter BS, DellaGrotta SA, Helderman J, Kilbride H, Loncar CM, McGowan E, Neal CR, O’Shea TM, Pastyrnak SL, Sheinkopf SJ, Lester BM. Preeclampsia, Fetal Growth Restriction, and 24-Month Neurodevelopment in Very Preterm Infants. JAMA Netw Open. 2024; 7(7): e2420382.

IMPORTANCE: Preeclampsia has direct influences on a developing fetus and may impact postnatal health, and fetal growth restriction (FGR) is often seen co-occurring with preeclampsia. The development of children born very preterm after preeclampsia diagnosis with and without FGR is not well characterized. OBJECTIVE: To examine the associations of preeclampsia and FGR with developmental and/or behavioral outcomes in a cohort of very preterm infants. DESIGN, SETTING, AND PARTICIPANTS: In this cohort study, infants in the prospective Neonatal Neurobehavior and Outcomes in Very Preterm Infants study were enrolled between April 2014 and June 2016 from 9 US university-affiliated neonatal intensive care units (NICUs). Eligible infants were born before 30 weeks’ gestation. Infants were excluded for any major congenital anomalies and for maternal age younger than 18 years or cognitive impairment impacting the ability to provide informed consent. Data analysis was performed from November 2023 to January 2024. EXPOSURE: Maternal preeclampsia and FGR in very preterm infants. MAIN OUTCOMES AND MEASURES: The Bayley-III cognition, motor, and language scores less than 85 (-1 SD) indicated developmental delay. Child Behavior Checklist/Preschool 1.5-5 T-scores greater than or equal to 64 for internalizing, externalizing, or total problems indicated clinical importance. RESULTS: Of 704 infants enrolled, 529 (mean [SD] gestational age, 27.0 [1.9] weeks; 287 male [54.3%]) were studied at 24-month follow-up. A total of 94 infants’ mothers had preeclampsia (23.2%), and 46 infants (8.7%) had FGR. In adjusted models, preeclampsia was not associated with Bayley-III (cognitive, B = 3.43 [95% CI, -0.19 to 6.66]; language, B = 3.92 [95% CI, 0.44 to 7.39]; motor, B = 1.86 [95% CI, -1.74 to 5.47]) or Child Behavior Checklist/Preschool 1.5-5 (internalizing, B = -0.08 [95% CI, -2.58 to 2.73]; externalizing, B = 0.69 [95% CI, -1.76 to 3.15]; total, B = 0.21 [95% CI, -2.48 to 2.91]) outcomes. FGR was associated with significantly lower Bayley-III scores (cognitive, B = -8.61 [95% CI, -13.33 to -3.89]; language, B = -8.29 [95% CI, -12.95 to -3.63]; motor, B = -7.60 [95% CI, -12.40 to -2.66]), regardless of preeclampsia status. CONCLUSIONS AND RELEVANCE: In this cohort study of preterm infants, preeclampsia was not associated with developmental and/or behavioral outcomes, but infants with FGR may be prone to developmental delays. These findings suggest future areas of research for understanding the roles of preeclampsia and FGR separately and together in early child development for preterm infants.

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7. Cross L, Belshaw F, Piovesan A, Atherton G. Game Changer: Exploring the Role of Board Games in the Lives of Autistic People. J Autism Dev Disord. 2024.

This mixed methods paper reports findings from three studies examining the overlap between autism and hobbyist board gaming. The first was a quantitative survey of over 1600 board gamers, showing that autistic individuals are overrepresented in this hobby compared to the general population and that autistic traits measured by the AQ are significantly elevated amongst board gamers. Study 1 also assessed gamers’ motivations and preferences and reported key differences as well as similarities between autistic and non-autistic gamers. The second was a qualitative study that reported the results of 13 interviews with autistic individuals who are hobbyist board gamers. Using Interpretive Phenomenological Analysis (IPA), four key themes were uncovered, including a preference for systemising, escapism and passions, the social lubrication effect of games and difficulties with deception. In the third, 28 autistic individuals were introduced to board games in groups of 5-10 over an afternoon. Subsequent focus groups were then analysed using IPA. This analysis uncovered themes around how board games are challenging but encouraged growth and how they were an alternative vehicle for forging social relationships. Through this paper, we discuss how and why board games may be a popular hobby amongst the autistic population, and its potential utility for improving autistic wellbeing.

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8. Danieli PP, Hoang N, Selvanayagam T, Yang A, Breetvelt E, Tabbers M, Cohen C, Aelvoet AS, Trost B, Ward T, Semotiuk K, Durno C, Aronson M, Cohen Z, Dekker E, Vorstman J. Autistic traits in youth with familial adenomatous polyposis: A Dutch-Canadian case-control study. Am J Med Genet B Neuropsychiatr Genet. 2024: e32999.

This study investigated the neurodevelopmental impact of pathogenic adenomatous polyposis coli (APC) gene variants in patients with familial adenomatous polyposis (FAP), a cancer predisposition syndrome. We hypothesized that certain pathogenic APC variants result in behavioral-cognitive challenges. We compared 66 FAP patients (cases) and 34 unaffected siblings (controls) to explore associations between APC variants and behavioral and cognitive challenges. Our findings indicate that FAP patients exhibited higher Social Responsiveness Scale (SRS) scores, suggesting a greater prevalence of autistic traits when compared to unaffected siblings (mean 53.8 vs. 47.4, Wilcoxon p = 0.018). The distribution of SRS scores in cases suggested a bimodal pattern, potentially linked to the location of the APC variant, with scores increasing from the 5′ to 3′ end of the gene (Pearson’s r = 0.33, p = 0.022). While we observed a trend toward lower educational attainment in cases, this difference was not statistically significant. This study is the first to explore the connection between APC variant location and neurodevelopmental traits in FAP, expanding our understanding of the genotype-phenotype correlation. Our results emphasize the importance of clinical assessment for autistic traits in FAP patients, shedding light on the potential role of APC gene variants in these behavioral and cognitive challenges.

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9. Dou JF, Schmidt RJ, Volk HE, Nitta MM, Feinberg JI, Newschaffer CJ, Croen LA, Hertz-Picciotto I, Fallin MD, Bakulski KM. Exposure to heavy metals in utero and autism spectrum disorder at age 3: a meta-analysis of two longitudinal cohorts of siblings of children with autism. Environ Health. 2024; 23(1): 62.

BACKGROUND: Autism spectrum disorder (ASD) is a prevalent and heterogeneous neurodevelopmental disorder. Risk is attributed to genetic and prenatal environmental factors, though the environmental agents are incompletely characterized. METHODS: In Early Autism Risk Longitudinal Investigation (EARLI) and Markers of Autism Risk in Babies Learning Early Signs (MARBLES), two pregnancy cohorts of siblings of children with ASD, urinary metals concentrations during two pregnancy time periods (< 28 weeks and ≥ 28 weeks of gestation) were measured using inductively coupled plasma mass spectrometry. At age three, clinicians assessed ASD with DSM-5 criteria. In an exposure-wide association framework, using multivariable log binomial regression, we examined each metal for association with ASD status, adjusting for gestational age at urine sampling, child sex, age at pregnancy, race/ethnicity and education. We meta-analyzed across the two cohorts. RESULTS: In EARLI (n = 170) 17% of children were diagnosed with ASD, and 44% were classified as having non-neurotypical development (Non-TD). In MARBLES (n = 231), 21% were diagnosed with ASD, and 14% classified as Non-TD. During the first and second trimester period (< 28 weeks), having cadmium concentration over the level of detection was associated with 1.69 (1.08, 2.64) times higher risk of ASD, and 1.29 (0.95, 1.75)times higher risk of Non-TD. A doubling of first and second trimester cesium concentration was marginally associated with 1.89 (0.94, 3.80) times higher risk of ASD, and a doubling of third trimester cesium with 1.69 (0.97, 2.95) times higher risk of ASD. CONCLUSION: Exposure in utero to elevated levels of cadmium and cesium, as measured in urine collected during pregnancy, was associated with increased risk of developing ASD.

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10. Farzanegan F, Shadmehri SA, Shooshtari Z, Hamidi AR, Shahri A. Evaluating malocclusion patterns in children with autism spectrum disorder using the index of complexity, outcome and need: a cross-sectional study. BMC Oral Health. 2024; 24(1): 759.

BACKGROUND: The purpose of this study was to evaluate the complexity of malocclusion and existing patterns in children with autism spectrum disorders (ASD) using the index of complexity, outcome and need (ICON). METHODS: This cross-sectional study included children diagnosed with ASD, aged 9-15 years. A group of healthy children with the same demographic characteristics was randomly selected as the control group. Malocclusion was assessed according to ICON scoring protocol. The following parameters were recorded: dental aesthetics, upper arch crowding/spacing, presence of crossbite, anterior-vertical relationship (open and deep bite) and buccal segment anterior-posterior relationship. Finally, an overall ICON score was derived and reported for each patient. Descriptive analysis was performed for all investigated variables. Significance level was set at p < 0.05. RESULTS: A total of 324 children, divided into ASD (162) and control (162) groups, comprised the study population. Our results demonstrated that the average overall ICON score was significantly higher in the ASD group compared to the control group (38.77 vs. 27.43, p < 0.001). ASD children also obtained significantly higher scores regarding the dental aesthetics component (3.84 vs 2.78, p < 0.001). Study groups were significantly different in terms of the prevalence of incisor overbite and open bite (p = 0.002 and p < 0.001, respectively). Patients in the ASD group showed a higher prevalence of Class II and Class III malocclusions (p < 0.001). CONCLUSION: ASD children obtained significantly higher overall ICON scores, indicating more complex and severe malocclusions. These children also exhibited a greater tendency towards Class II and III malocclusions.

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11. Greene A, Baugh M, Sherwood-Laughlin C, Greathouse L, Galyan J, Simic Stanjovic I, Sangmo D, Jozkowski K, Dubie M, Chow A. Development of a sexual consent intervention for adolescents with intellectual and developmental disabilities. J Appl Res Intellect Disabil. 2024; 37(5): e13272.

BACKGROUND: Tailored sexuality education for adolescents with intellectual and developmental disabilities is a crucial, yet unmet, need as this population is particularly at risk for sexual abuse and victimisation. However, there are no evidence-based interventions to specifically address this need. This paper presents the development of an intervention framework to address equity in sexuality education and support adolescents with intellectual and developmental disabilities to understand and provide sexual consent, a foundational aspect of sexuality education and sexual health. METHODS: The Sexual Health Equity Project team used a Community-Based Participatory Research approach to develop a four-module sexual consent intervention for adolescents with intellectual and developmental disabilities. We leveraged a diverse, interdisciplinary team in a suburban Midwestern school district, and used Backward Design to create objectives and assessments which were rooted in findings from qualitative data by special education teachers. RESULTS: The resulting sexual consent intervention, Ask Me First-Choices, is comprised of four modules covering topics including definition of sexual consent; decision-making strategies and practice; communicating consent and refusal, identifying situations of consent and non-consent; and legal issues surrounding consent. Each module is divided into five components for content delivery: (1) introduction, (2) lecture, (3) supplemental activity, (4) assessment, and (5) conclusion. We detail the intervention’s unique aspects, emphasising areas where we used Universal Design for Learning principles to support teachers’ instruction and students’ learning. CONCLUSION: Our efforts to create a sexual consent intervention directly address sexuality education equity issues. We offer commentary on our design process and decisions, as well as recommendations for future groups who want to develop sexual health interventions in similar contexts for students with intellectual and developmental disabilities. Next steps include further testing and validation of the sexual consent intervention to build the evidence-base of sexuality education for adolescents with intellectual and developmental disabilities.

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12. Herrera ML, Paraíso-Luna J, Bustos-Martínez I, Barco Á. Targeting epigenetic dysregulation in autism spectrum disorders. Trends Mol Med. 2024.

Autism spectrum disorders (ASD) comprise a range of neurodevelopmental pathologies characterized by deficits in social interaction and repetitive behaviors, collectively affecting almost 1% of the worldwide population. Deciphering the etiology of ASD has proven challenging due to the intricate interplay of genetic and environmental factors and the variety of molecular pathways affected. Epigenomic alterations have emerged as key players in ASD etiology. Their research has led to the identification of biomarkers for diagnosis and pinpointed specific gene targets for therapeutic interventions. This review examines the role of epigenetic alterations, resulting from both genetic and environmental influences, as a central causative factor in ASD, delving into its contribution to pathogenesis and treatment strategies.

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13. Jeon H, Hur A, Lee H, Shin YW, Lee SI, Shin CJ, Kim S, Ju G, Lee J, Jung JH, Chung S, Son JW. The Relationship Between Brain Activation for Taking Others’ Perspective and Interoceptive Abilities in Autism Spectrum Disorder: An fMRI Study. Soa Chongsonyon Chongsin Uihak. 2024; 35(3): 197-209.

OBJECTIVES: In this functional magnetic resonance imaging study, we aimed to investigate the differences in brain activation between individuals with autism spectrum disorder (ASD) and typically developing (TD) individuals during perspective taking. We also examined the association between brain activation and empathic and interoceptive abilities. METHODS: During scanning, participants from the ASD (n=17) and TD (n=22) groups were shown pain stimuli and asked to rate the level of the observed pain from both self- and other-perspectives. Empathic abilities, including perspective taking, were measured using an empathic questionnaire, and three dimensions of interoception were assessed: interoceptive accuracy, interoceptive sensibility, and interoceptive trait prediction errors. RESULTS: During self-perspective taking, the ASD group exhibited greater activation in the left precuneus than the TD group. During other-perspective taking, relative hyperactivation extended to areas including the right precuneus, right superior frontal gyrus, left caudate nucleus, and left amygdala. Brain activation levels in the right superior frontal gyrus while taking other-perspective were negatively correlated with interoceptive accuracy, and those in the left caudate were negatively correlated with perspective taking ability in the ASD group. CONCLUSION: Individuals with ASD show atypical brain activation during perspective taking. Notably, their brain regions associated with stress reactions and escape responses are overactivated when taking other-perspective. This overactivity is related to poor interoceptive accuracy, suggesting that individuals with ASD may experience difficulties with the self-other distinction or atypical embodiment when considering another person’s perspective.

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14. Journal F, Franchini M, Godel M, Kojovic N, Latrèche K, Solazzo S, Schneider M, Schaer M. Phenotyping variability in early socio-communicative skills in young children with autism and its influence on later development. Autism Res. 2024.

Children with autism spectrum disorder (ASD) often face challenges in early social communication skills, prompting the need for a detailed exploration of specific behaviors and their impact on cognitive and adaptive functioning. This study aims to address this gap by examining the developmental trajectories of early social communication skills in preschoolers with ASD aged 18-60 months, comparing them to age-matched typically developing (TD) children. Utilizing the early social communication scales (ESCS), the research employs a longitudinal design to capture changes over time. We apply a principal component analysis (PCA) to ESCS variables to identify underlying components, and cluster analysis to identify subgroups based on preverbal communication profiles. The results reveal consistent differences in early social communication skills between ASD and TD children, with ASD children exhibiting reduced skills. PCA identifies two components, distinguishing objects-directed behaviors and social interaction-directed behaviors. Cluster analysis identifies three subgroups of autistic children, each displaying specific communication profiles associated with distinct cognitive and adaptive functioning trajectories. In conclusion, this study provides a nuanced understanding of early social communication development in ASD, emphasizing the importance of low-level behaviors. The identification of subgroups and their unique trajectories contributes to a more comprehensive understanding of ASD heterogeneity. These findings underscore the significance of early diagnosis, focusing on specific behaviors predicting cognitive and adaptive functioning outcomes. The study encourages further research to explore the sequential development of these skills, offering valuable insights for interventions and support strategies.

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15. Kim Y, Jeong M, Koh IG, Kim C, Lee H, Kim JH, Yurko R, Kim IB, Park J, Werling DM, Sanders SJ, An JY. CWAS-Plus: estimating category-wide association of rare noncoding variation from whole-genome sequencing data with cell-type-specific functional data. Brief Bioinform. 2024; 25(4).

Variants in cis-regulatory elements link the noncoding genome to human pathology; however, detailed analytic tools for understanding the association between cell-level brain pathology and noncoding variants are lacking. CWAS-Plus, adapted from a Python package for category-wide association testing (CWAS), enhances noncoding variant analysis by integrating both whole-genome sequencing (WGS) and user-provided functional data. With simplified parameter settings and an efficient multiple testing correction method, CWAS-Plus conducts the CWAS workflow 50 times faster than CWAS, making it more accessible and user-friendly for researchers. Here, we used a single-nuclei assay for transposase-accessible chromatin with sequencing to facilitate CWAS-guided noncoding variant analysis at cell-type-specific enhancers and promoters. Examining autism spectrum disorder WGS data (n = 7280), CWAS-Plus identified noncoding de novo variant associations in transcription factor binding sites within conserved loci. Independently, in Alzheimer’s disease WGS data (n = 1087), CWAS-Plus detected rare noncoding variant associations in microglia-specific regulatory elements. These findings highlight CWAS-Plus’s utility in genomic disorders and scalability for processing large-scale WGS data and in multiple-testing corrections. CWAS-Plus and its user manual are available at https://github.com/joonan-lab/cwas/ and https://cwas-plus.readthedocs.io/en/latest/, respectively.

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16. McNally Keehn R, Rispoli M, Saina C, Nafiseh A, Oyungu E, Omari FW, Kigen B, Hassinger T, Stewart L, Gross J, McHenry M. Pepea Pamoja:(†) Applying the Ecological Validity Framework to co-develop a wellbeing and behavioural training program for caregivers of young children with autism in low-resource settings of Kenya and the United States. Child Care Health Dev. 2024; 50(4): e13299.

BACKGROUND: Autism is a complex neurodevelopmental disability with global prevalence of one in 100 individuals. Poor access to interventions in both under-resourced regions of high-income countries and low- and middle-income countries has deleterious effects on the health and wellbeing of individuals with autism and their families. Our objective was to utilize a reciprocal innovation framework and participatory methods to adapt and co-develop a culturally grounded group-based wellbeing and naturalistic developmental behavioural intervention (NDBI) training program for caregivers of young children with autism to be implemented in Kenya and rural Indiana. METHODS: This study was conducted within the Academic Model Providing Access to Healthcare (AMPATH) program. An evidence-informed Naturalistic Developmental Behavioral Intervention (NDBI) previously utilized in Indiana was adapted and iteratively refined using the Ecological Validity Framework (EVF) by a team of US and Kenyan disability experts. Key adaptations to the program were made across the EVF domains of language, persons, metaphors/content, concepts, goals, methods, and context. RESULTS: Substantial cultural adaptations were made to the NDBI following the EVF model, including the addition of traditional Kenyan cultural practices, use of narrative principles, and focus on daily routines over play. Pepea, the adapted program, involves 10 group sessions covering content in basic education on autism, positive caregiver coping strategies, and behavioural skills training to promote child communication and reduce challenging behaviour. Key adaptations for Pepea were integrated back into a US NDBI caregiver training program. CONCLUSIONS: This study fills a critical gap by detailing the adaptation process of a caregiver wellbeing and naturalistic developmental behavioural training program for caregivers of children with autism in low-resource settings. Our next steps are to report on mixed-methods outcomes from pilot implementation. Our long-term goal is to apply these insights to advance sustainable and scalable autism intervention services across the globe.

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17. Miles KD, Barker CM, Russell KP, Appel BH, Doll CA. Electrical synapses mediate embryonic hyperactivity in a zebrafish model of Fragile X syndrome. J Neurosci. 2024.

Although hyperactivity is associated with a wide variety of neurodevelopmental disorders, the early embryonic origins of locomotion have hindered investigation of pathogenesis of these debilitating behaviors. The earliest motor output in vertebrate animals is generated by clusters of early-born motor neurons that occupy distinct regions of the spinal cord, innervating stereotyped muscle groups. Gap junction electrical synapses drive early spontaneous behavior in zebrafish, prior to the emergence of chemical neurotransmitter networks. We use a genetic model of hyperactivity to gain critical insight into the consequences of errors in motor circuit formation and function, finding that Fragile X syndrome (FXS) model mutant zebrafish are hyperexcitable from the earliest phases of spontaneous behavior, show altered sensitivity to blockade of electrical gap junctions, and have increased expression of the gap junction protein Connexin 34/35. We further show that this hyperexcitable behavior can be rescued by pharmacological inhibition of electrical synapses. We also use functional imaging to examine motor neuron and interneuron activity in early embryogenesis, finding genetic disruption of electrical gap junctions uncouples activity between mnx1 (+) motor neurons and interneurons. Taken together, our work highlights the importance of electrical synapses in motor development and suggests that the origins of hyperactivity in neurodevelopmental disorders may be established during the initial formation of locomotive circuits.Significance Statement The origins of hyperactivity in neurodevelopmental disorders are difficult to pinpoint in vertebrate systems. Zebrafish locomotive circuits initiate in early embryogenesis, with defined motor neurons and interneurons driving the earliest locomotive movements. Using a genetic model of hyperactivity, we show that Fragile X syndrome model fmr1 mutant embryos display hyperexcitable behavior and express excess gap junction connexin proteins on motor circuit neurons. We further show that this hyperexcitable behavior can be rescued by pharmacological inhibition of electrical synapses. Taken together, this data suggests hyperactive behavior initiates in the earliest phases of neurodevelopment.

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18. Rahdar M, Davoudi S, Dehghan S, Javan M, Hosseinmardi N, Behzadi G, Janahmadi M. Reversal of electrophysiological and behavioral deficits mediated by 5-HT7 receptor upregulation following LP-211 treatment in an autistic-like rat model induced by prenatal valproic acid exposure. Neuropharmacology. 2024; 257: 110057.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by alterations and imbalances in multiple brain neurochemical systems, particularly the serotonergic neurotransmission. This includes changes in serotonin (5-HT) levels, aberrations in 5-HT transporter activity, and decreased synthesis and expression of 5-HT receptors (5-HT7Rs). The exact role of the brain 5-HT system in the development of ASD remains unclear, with conflicting evidence on its involvement. Recently, we have reported research has shown a significant decrease in serotonergic neurons originating from the raphe nuclei and projecting to the CA1 region of the dorsal hippocampus in autistic-like rats. Additionally, we have shown that chronic activation of 5-HT7Rs reverses the effects of autism induction on synaptic plasticity. However, the functional significance of 5-HT7Rs at the cellular level is still not fully understood. This study presents new evidence indicating an upregulation of 5-HT7R in the CA1 subregion of the hippocampus following the induction of autism. The present account also demonstrates that activation of 5-HT7R with its agonist LP-211 can reverse electrophysiological abnormalities in hippocampal pyramidal neurons in a rat model of autism induced by prenatal exposure to VPA. Additionally, in vivo administration of LP-211 resulted in improvements in motor coordination, novel object recognition, and a reduction in stereotypic behaviors in autistic-like offspring. The findings suggest that dysregulated expression of 5-HT7Rs may play a role in the pathophysiology of ASD, and that agonists like LP-211 could potentially be explored as a pharmacological treatment for autism spectrum disorder.

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19. Reisinger DL, Goodwin MS, Horn PS, Schmitt LM, Coffman MC, Shaffer RC. Examining the feasibility and utility of heart rate variability on intervention outcomes targeting emotion regulation in autism: a brief report. Sci Rep. 2024; 14(1): 15409.

Autistic youth experience several behavioral and emotional characteristics that can predispose them to emotion dysregulation (ED). Current literature examining ED in autism spectrum disorder (ASD) is limited to parent- and self-reported measures, indicating a need for biological or physiological methods to better assess emotion regulation in ASD. Utilizing the autonomic nervous system, specifically heart rate variability (HRV), may be a promising method to objectively measure ED in ASD, given it is one of the body’s primary means of regulating physiological arousal. Our pilot study is one of the first to examine the feasibility, utility, and construct validity of HRV along with clinical measures within an intervention targeting ED-specific symptoms in ASD. Participants included 30 autistic youth ages 8-17 years who participated in the pilot study of Regulating Together, a group-based intervention targeting emotion regulation. We demonstrate HRV is feasible, demonstrates adequate test-retest reliability, and is complimentary to clinician- and parent-reported measures. Our preliminary findings also point to certain HRV profiles being indicative of long-term outcomes after receiving treatment. HRV may be a useful, objective tool in determining differential needs of long-term follow-up care for treatment maintenance at screening or baseline stages.

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20. Rispoli KM, Curtiss SL, Naguib S. Brief transition-focused education for families of autistic youth: preliminary mixed-methods investigation. Disabil Rehabil. 2024: 1-9.

PURPOSE: The transition to adulthood is one of the most challenging and complex processes for autistic youth and their families. Few evidence-based transition support programs exist, and those that have garnered support require long-term commitments and resources that may prohibit participation by families with financial and time limitations. The current study investigated the feasibility and initial promise of a brief, caregiver-focused educational transition program for families of autistic youth delivered in the community over a single day. METHODS: Quantitative informant-report and qualitative interview data were collected from 12 caregivers of autistic youth before and after program participation. Using a partially mixed sequential equal status design, quantitative and qualitative data were integrated to evaluate change in caregiver transition knowledge and empowerment, as well as caregivers’ perceptions of program feasibility, acceptability, and usefulness. RESULTS: Caregivers reported significant increases in knowledge of transition-related topics and sense of empowerment regarding their family life. Caregiver perceptions of the intervention suggest they found it feasible, acceptable, and useful. CONCLUSIONS: Short-term transition programming may be a helpful option for caregivers who seek transition supports for autistic youth. The transition to adulthood is a stressful and complex process for autistic adolescents and their caregivers.Many caregivers lack time, financial resources, and access to comprehensive transition supports.Brief educational support is a potential alternative for aiding caregivers in planning for and assisting with adolescents’ postsecondary training/education, employment, social, and living arrangements.The Planning for your Loved Ones Future (PLOF) intervention showed promise in improving caregiver knowledge about transition and sense of empowerment, and was described as feasible, accessible, and helpful by those who participated in a pilot study. eng.

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21. Rozenblat S, Nitzan T, Matz Vaisman T, Shusel R, Rum Y, Ashtamker M, Golan O, Dinstein I, Koller J. Autistic children and their parents in the context of war: Preliminary findings. Stress Health. 2024: e3442.

While existing literature on the intersection of trauma and autism is limited, emerging evidence suggests heightened vulnerability of autistic children to the psychological consequences of traumatic events, including an elevated risk of developing posttraumatic stress disorder (PTSD). Additionally, parents of autistic children often experience elevated levels of negative emotional states, compared to parents of typically developing children. This study investigates the impact of terrorism and war on autistic and non-autistic children and their parents, presenting preliminary results from the initial data collection phase of a year-long longitudinal investigation of the experience of autistic children and their parents following Hamas’ 7 October 2023 attack on Israel. Data gathered within 30 days of the initial attack reveal that both autistic and non-autistic children exhibited clinically significant post-traumatic stress symptoms, with autistic children demonstrating a more pronounced manifestation. Moreover, parents of autistic children reported significantly higher levels of depression, anxiety, and stress in the aftermath of the events, compared to an independent cohort of parents of autistic children assessed prior to the crisis. These results underscore the heightened susceptibility of autistic children to post-traumatic stress and the unique challenges confronted by their parents during times of conflict. The study highlights the imperative for tailored support services for autistic children and their families amidst traumatic incidents and stresses the need for further research in comparable contexts globally.

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22. Salabura C, Sourty A, Bat-Pitault F, Regnery K, Mayen S, Colson S. [Pain assessment for children and adolescents with autism spectrum disorders (ASD): A systematic review]. Encephale. 2024.

OBJECTIVE: Pain in children and adolescents with autism spectrum disorders remains underdiagnosed due to their inherent communication difficulties. The goal of this review is to identify the most suitable methods for assessing pain in this population and for evaluating the specific perceptions of, or behavioural reactions to, pain whilst considering disorder severity and specifiers (with or without accompanying intellectual impairment, with or without accompanying language impairment). METHOD: A systematic review and analysis of the international literature was conducted. RESULTS: Fourteen studies were selected. No difference was found in pain-related behaviours based on the age or gender of children or adolescents with autism. Three studies showed pain-related behaviours in autism spectrum disorders to be similar to control groups. Other studies showed specific behavioural responses in autism spectrum disorders with a longer physiological and behavioural recovery time associated with an episode of acute pain in this population. Similarly, the three studies that focused on sensory perceptions of pain all showed differences in the autism spectrum disorders population compared to control groups. In hospital or daily life contexts, studies essentially showed idiosyncratic expressions, hypervigilance, motor agitation, negative emotional reactions, or vocalizations. Regarding the association of autism severity with hyposensitivity to pain, the results remain unclear even when language disorders or intellectual disabilities are also present (in conjunction with autism). The Non-Communicative Children Pain Checklist and its translation into French and Italian showed good internal validity and was used by almost half of the studies in hetero-assessment, mostly by parents. Studies recommend the inclusion of parents in the assessment in order to optimise the evaluation process. Similarly, analysis of parent/child/caregiver interviews from the studies highlights the importance of personalizing pain assessment of children and adolescents, taking into account subject-specific characteristics, pathology, and context. CONCLUSION: An integrative and personalized approach to pain assessment appears to be the most appropriate for enhancing the understanding and detection of pain in individuals with autism spectrum disorders. This approach aligns well with a care setting where a nominated professional with a good expertise in autism is responsible for pain assessment. Given the complexity of identifying pain in individuals with autism, further qualitative studies, in conjunction with new pain exploration technologies, are considered necessary as well as a more extensive categorization of the population studies.

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23. Scacchi S, Pavarino LF, Mazzanti A, Trancuccio A, Priori SG, Colli Franzone P. Transmural APD heterogeneity determines ventricular arrhythmogenesis in LQT8 syndrome: Insights from Bidomain computational modeling. PLoS One. 2024; 19(7): e0305248.

Long QT Syndrome type 8 (LQT8) is a cardiac arrhythmic disorder associated with Timothy Syndrome, stemming from mutations in the CACNA1C gene, particularly the G406R mutation. While prior studies hint at CACNA1C mutations’ role in ventricular arrhythmia genesis, the mechanisms, especially in G406R presence, are not fully understood. This computational study explores how the G406R mutation, causing increased transmural dispersion of repolarization, induces and sustains reentrant ventricular arrhythmias. Using three-dimensional numerical simulations on an idealized left-ventricular model, integrating the Bidomain equations with the ten Tusscher-Panfilov ionic model, we observe that G406R mutation with 11% and 50% heterozygosis significantly increases transmural dispersion of repolarization. During S1-S4 stimulation protocols, these gradients facilitate conduction blocks, triggering reentrant ventricular tachycardia. Sustained reentry pathways occur only with G406R mutation at 50% heterozygosis, while neglecting transmural heterogeneities of action potential duration prevents stable reentry, regardless of G406R mutation presence.

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24. Schembri E, Jouve E, Poinso F, Encely L, Viellard M, Fernandez A, Guivarch J. Evaluation of a medically coordinated care program in the management of autism. Encephale. 2024.

Autism spectrum disorders (ASD) are neurodevelopmental disorders of varying intensity and disability. The reference health strategy in France for the care of young children with autism is day care hospital (DCH). As the number of places in DCH is insufficient, medically coordinated care programs by the mental health consultation centers (MHCC) are being developed in response. OBJECTIVES: Our objective is to evaluate the effectiveness of a medically coordinated care program in a MHCC versus the care in DCH of child psychiatry. METHODS: Non-inferiority retrospective study comparing the evolution after one year of care of 20 ASD children divided into two groups DCH and MHCC. In the DCH ASD group, the child is taken care of two half-days a week in a day hospital with individual educational care. In the MHCC ASD group, the child benefits from a medically coordinated care program. The medical care is reinforced by more frequent and longer consultations with guidance offered to parents. In both groups, the child receives speech therapy and psychomotor therapy in private practice at the same rate. Comparison is made using a composite criterion associating CARS-2 and VABS-II. Non-inferiority of the medically coordinated care program in autism in reference to DCH was tested on the difference between the changes (DCH group variation – MHCC group variation) with a non-inferiority threshold of 10% of the initial value of each score. RESULTS: We observed a reduction in autism severity at the CARS-2 and a moderate improvement in socio-adaptive behavior at the VABS-II in both groups. This trend was even more pronounced in the MHCC group than in the DCH group, but only the greater reduction in CARS-2 severity in the MHCC was statistically significant. CONCLUSIONS: As it is necessary to integrate the two scales into the composite criterion, it is not possible to retain the non-inferiority of the MHCC with care program. However, both those children followed in DCH and those in the MHCC care program progress. This shows the relevance of the care offered at the MHCC for children suffering from ASD, in the context of a growing lack of space in DCH. The continuation of this research work through multicenter studies with larger numbers could demonstrate the non-inferiority of coordinated care programs in the MHCC versus DCH. It would also allow subgroups to be set up, taking into account the initial characteristics of the children in order to have more precise indications concerning the relevance of each treatment.

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25. Stalford D, Graham S, Keenan M. A Discussion of Positive Behavior Support and Applied Behavior Analysis in the Context of Autism Spectrum Disorder in the UK and Ireland. Behav Anal Pract. 2024; 17(2): 442-55.

This article addresses the relationship between applied behavior analysis (ABA) and the emergence of positive behavior support (PBS) in context of autism spectrum disorder (ASD) in the UK and Ireland. Two overarching issues that are salient in this discussion are professional training and certification. To date, there has been a lack of standardized training or statutory requirements to practice PBS despite proponents insisting that its practice should be grounded in behavior analytic principles. Furthermore, there is an undercurrent of anti-ABA bias fueled by misinterpretation and unsubstantiated anecdotal claims used to promote an alternative « value based » approach to managing behavior.

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26. Swain D, Li Y, Brown HR, Petkova E, Lord C, Rogers SJ, Estes A, Kasari C, Kim SH. Implementing a Uniform Outcome Measurement Approach for Early Interventions of Autism Spectrum Disorders. J Am Acad Child Adolesc Psychiatry. 2024.

OBJECTIVE: Naturalistic developmental behavioral interventions (NDBI) for children with autism spectrum disorder (ASD) show evidence for effectiveness for specific social communication targets such as joint attention or engagement. However, combining evidence from different studies and comparing intervention effects across those studies have not been feasible due to lack of a standardized outcome measure of broader social communication skills that can be applied uniformly across trials. This investigation examines the usefulness of the Brief Observation of Social Communication Change (BOSCC) as a common outcome measure of general social communication skills based on secondary analyses of data obtained from previously conducted randomized control trials (RCTs) of three intervention models, the Early Social Intervention (ESI), Early Start Denver Model (ESDM) and Joint Attention Symbolic Play Engagement and Regulation (JASPER). METHOD: The subset of datasets from the three RCTs was created to examine differences in the BOSCC scores between intervention and control groups over the course of the interventions. RESULTS: Based on 582 videos from 207 caregiver-child dyads, the BOSCC noted significant differences between intervention vs. control groups in broad social communication skills within two of the three intervention models which were longer in duration and focused on a broad range of developmental skills. CONCLUSION: The BOSCC offers the potential to take a uniform measurement approach across different intervention models to capture the effect of intervention on general social communication skills but may not pick up the effects of some brief interventions targeting proximal outcomes.

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27. Townsend DB, Brothers KJ, MacDuff GS, Freeman A, Fry C, Rozenblat E, DeFeo D, Budzinska A, Ruta-Sominka I, Birkan B, Hall LJ, Krantz PJ, McClannahan LE. Alliance for Scientific Autism Intervention: System Components and Outcome Data from High-Quality Service Delivery Organizations. Behav Anal Pract. 2024; 17(2): 565-80.

Promoting excellence in autism intervention is arguably more urgent than ever for the field of applied behavior analysis. To fulfill this objective, autism agencies must operate from validated program systems and do so with fidelity. Program components include, but are not limited to, staff training and evaluation of clinical skills, functional personnel roles designed to promote positive outcomes for those served, and professional staff-communication-skill repertoires. Data on client outcomes must be tied to implementation of core program variables; and, contingencies between the data on client outcomes and staff performance must exist. Furthermore, these contingencies must be yoked across members of the organization to ensure a sustainable and effective program model. Finally, data on consumer satisfaction must be collected and used to evaluate program components and agency practices. Members of the Alliance for Scientific Autism Intervention have implemented key program-wide systems based upon the work of McClannahan and Krantz Journal of Applied Behavior Analysis, 26, 589-596 (1993) for decades and across various agency cultures. Data collected by six independent educational agencies on client outcomes, program implementation, and consumer feedback for a 10-year time span demonstrate the sustainability of the model and support the importance of key organizational systems and the relationship between implementation of the model and high-quality outcomes for individuals with autism.

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28. Vasconcelos C, Perry IS, Gottfried C, Riesgo R, Castro K. Folic acid and autism: updated evidences. Nutr Neurosci. 2024: 1-35.

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition that impairs communication, socialization, and behavior. The association of ASD with folic acid has been investigated due to the importance of this vitamin for neurological health. This study is an update of the publication ‘Folic acid and autism: What do we know?’ and aims to systematically review studies examining the relationship between folic acid and ASD. The search resulted in 2,389 studies on folic acid and ASD, which were selected by two reviewers based on their titles and abstracts. Studies meeting the inclusion criteria were fully read. The 52 included studies involved 10,429 individuals diagnosed with ASD and assessed the intake of vitamin B6, folic acid, and vitamin B12; serum levels of these vitamins, homocysteine, and methionine; therapeutic interventions using folic acid; and the association between maternal exposure to this vitamin and the risk of ASD. The evidence of insufficient folic acid intake in most individuals with ASD remains consistent in this update. No association was found between maternal exposure to folic acid and the risk of ASD in their children. Despite observed improvements in communication, socialization, and behavior in individuals with ASD following folic acid interventions, it is crucial to consider the individuality and complexity of ASD. Given the relevance of the topic, there remains a need for more high-quality research and clinical trials characterized by rigorous methodological designs.

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29. Wu Z, Lam C, To CKS. Spontaneous Generation of Unconventional Language and Its Link with Grammatical Performance in Chinese Adults With and Without ASD. J Autism Dev Disord. 2024.

This study investigated the generation of unconventional language in the spontaneous speech of Chinese adults with autism spectrum disorder (ASD), and how it was related to their grammatical performance, when compared to neurotypical (NT) controls. Twenty Cantonese-speaking adults with ASD and 20 NT controls completed three interview tasks in the Autism Diagnostic Observation Schedule, Second Edition (ADOS-2), and their spontaneous speech was recorded and transcribed. Utterances containing unconventional language (neologisms, idiosyncratic phrases, and pedantic language), morphosyntactic errors, mean length of utterance (MLU), and mazes were computed. The ASD group produced more neologisms, idiosyncratic phrases, and pedantic language than the NT group and their grammatical difficulties were shown in shorter MLU but not morphosyntactic errors. Mazes were more frequent in the ASD than the NT group. While the use of unconventional language increased with MLU in the NT group, it correlated positively with mazes in the ASD group. Generation of unconventional language, particularly pedantic language, in Cantonese-speaking NT adults is linked to more advanced grammar, while it appears to be a common speech characteristic among autistic speakers regardless of individual grammatical performance.

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30. Xiao J, Zhu H, Kong W, Jiang X, Wu C, Chen JG, Li X. Stabilizing axin leads to optic nerve hypoplasia in a mouse model of autism. Exp Eye Res. 2024; 245: 109988.

Autism spectrum disorder (ASD) is a group of neurodevelopment disorders characterized by deficits in social interaction and communication, and repetitive or stereotyped behavior. Autistic children are more likely to have vision problems, and ASD is unusually common among blind people. However, the mechanisms behind the vision disorders in autism are unclear. Stabilizing WNT-targeted scaffold protein Axin2 by XAV939 during embryonic development causes overproduction of cortical neurons and leads to autistic-like behaviors in mice. In this study, we investigated the relationship between vision abnormality and autism using an XAV939-induced mouse model of autism. We found that the mice receiving XAV939 had decreased amplitude of bright light-adaptive ERG. The amplitudes and latency of flash visual evoked potential recorded from XAV939-treated mice were lower and longer, respectively than in the control mice, suggesting that XAV939 inhibits visual signal processing and conductance. Anatomically, the diameters of RGC axons were reduced when Axin2 was stabilized during the development, and the optic fibers had defective myelin sheaths and reduced oligodendrocytes. The results suggest that the WNT signaling pathway is crucial for optic nerve development. This study provides experimental evidence that conditions interfering with brain development may also lead to visual problems, which in turn might exaggerate the autistic features in humans.

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